title: Prostaglandin E2 primes naive T cells for the production of anti-inflammatory cytokines.
abstract: In addition to their capacity to induce pain, vasodilatation and fever, prostaglandins E (PGE) exert anti-inflammatory activities by inhibiting the release of pro-inflammatory cytokines by macrophages and T cells, and by increasing interleukin (IL)-10 production by macrophages. We here report that PGE2, the major arachidonic acid metabolite released by antigen-presenting cells (APC), primes naive human T cells for enhanced production of anti-inflammatory cytokines and inhibition of pro-inflammatory cytokines. Unfractionated as well as CD45RO- CD31+ sort-purified neonatal CD4 T cells acquire the capacity to produce a large spectrum of cytokines after priming with anti-CD3 and anti-CD28 monoclonal antibodies (mAb), in the absence of both APC and exogenous cytokines. PGE2 primes naive T cells in a dose-dependent fashion for production of high levels of IL-4, IL-10 and IL-13, and very low levels of IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and TNF-beta. PGE2 does not significantly increase IL-4 production in priming cultures, whereas it suppresses IL-2 and IFN-gamma. Addition of a neutralizing mAb to IL-4 receptor in primary cultures, supplemented or not with PGE2, prevents the development of IL-4-producing cells but does not abolish the effects of PGE2 on IL-10 and IL-13 as well as T helper (Th)1-associated cytokines. Addition of exogenous IL-2 in primary cultures does not alter the effects of PGE2 on naive T cell maturation. Thus PGE2 does not act by increasing IL-4 production in priming cultures, and its effects are partly IL-4 independent and largely IL-2 independent. Together with the recent demonstration that PGE2 suppresses IL-12 production, our results strongly suggest that this endogenously produced molecule may play a significant role in Th subset development and that its stable analogs may be considered for the treatment of Th1-mediated inflammatory diseases.
authors.affiliation: Université de Montréal, Centre de Recherche Louis-Charles Simard, Hôpital Notre-Dame, Montréal, Canada. demeurec@magellan.umontreal.ca
authors.forename: C E
authors.initials: CE
authors.lastname: Demeure
authors.forename: L P
authors.initials: LP
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Desjardins
authors.forename: P
authors.initials: P
authors.lastname: Raynauld
authors.forename: G
authors.initials: G
authors.lastname: Delespesse
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*
chemical_list: D016207:Cytokines; D015232:Dinoprostone